Improved Scintillators for Time-of-Flight Positron Emission Tomography Project Summary/Abstract We propose to significantly improve the diagnostic imaging capability of positron emission tomography by finding new scintillators with the gamma-ray stopping power of Lu2SiO5:Ce (LSO) and the luminosity, timing, and energy resolution of LaBr3:Ce. Compared with LSO, improving the luminosity from 30,000 photons/MeV to 60,000 photons/MeV and reducing the decay time from 40 ns to 20 ns will improve the timing resolution by a factor of two and the effective time-of-flight (TOF) sensitivity by a factor of two. This is because the variance of the statistical noise in the reconstructed image is reduced by the same factor as the timing resolution. Moreover, improving the energy resolution from 9% to 4% will reduce the background from tissue-scattered photons by about a factor of two. These advances in technology will significantly improve the detection of disease, especially in obese patients and for gated imaging of the thorax, and will increase the ability to use repeat imaging to study the effects of therapy on the disease. The proposed research will focus on Ce3+ and Pr3+ activated lutetium compounds because (1) of the known high-luminosity scintillators, only those activated with Ce3+ and Pr3+ are fast enough to be considered for TOF and 3D PET (2) of the trivalent elements in the periodic table that can be substituted with Ce3+ and Pr3+ to produce highly luminous scintillators (Y, La, Gd, and Lu), lutetium provides the highest atomic number and (3) no known high-luminosity scintillator contains an element heavier than lutetium. Thus, lutetium compounds have the highest promise of having both high luminosity and good stopping power for 511 keV annihilation photons. There are hundreds of dense lutetium compounds that have never been explored as gamma-ray scintillation detectors. We propose to use the high- throughput facilities developed at LBNL to synthesize doped candidate compounds in microcrystalline form, characterize their emissions under X-ray excitation, grow crystals of the best candidates, and measure the their energy and timing resolution. The crystal size and shape, and the photodetector and electronics will be similar to those used in a positron emission tomograph. Approximately 2,000 microcrystalline powder samples (of 200 different doped compounds) will be synthesized and characterized, and approximately 50 crystals of the best will be grown and measured. First-principles and empirical theory will be used to prioritize the candidate lists. LBNL is in a unique position to perform this research because of the recent creation of (1) the high-throughput scintillator discovery facility (funded by DHS) and (2) the crystal growth facility (funded by DOE and DHS). These contain 48 synthesis furnaces, an X-ray diffractometer, a pulsed X-ray system, an X-ray luminescence spectrometer, and 14 crystal growing furnaces of three different types. The measurement instruments have computer-controlled sample changers and automatically upload their data to an on-line database. Note that DHS does not fund the development of lutetium scintillators due to their inherent radioactivity and DOE no longer funds nuclear medicine research at the National Laboratories. PUBLIC HEALTH RELEVANCE: Improved Scintillators for Time-of-Flight Positron Emission Tomography Project Narrative/Relevance the goal of the proposed research is the discovery of new radiation detector materials (scintillators) with an improved combination of photoelectric stopping power, timing resolution, and energy resolution compared with the detectors currently used in positron emission tomographs. This would allow these machines to produce 3D images of positron-emitting isotopes in the human body of higher quality and with lower radiation dose. The result is improved detection of disease and the ability to perform repeated studies of the effects of therapy on the disease.